The embodiments herein relate generally to uses for cross-linked hyaluronic acid.
Persistent or chronic pain is a worldwide problem affecting millions of people, including the patient and family, marriage, and employer. This places a huge burden upon a country's healthcare system, resulting in billions of dollars spent annually in diagnosis, treatment, surgery, medications, rehabilitation as well as lost wages and productivity. Embodiments of the present invention involve a new indication of cross-linked hyaluronic acid for treating pain.
As noted in U.S. Pat. No. 3,396,081 issued to Billek, hyaluronic acid is a naturally existing composition of matter that can be found in the eyes and umbilical cords of mammals and extracted in a number of ways including precipitation with acetone to create a dry powder.
As noted in U.S. Pat. No. 4,716,224 issued to Okuyama, cross-linked hyaluronic acid is obtainable by crosslinking hyaluronic acid with a polyfunctional epoxy compound selected from halomethyloxirane compounds, compounds of the formula:

wherein n is from 2 to 6, and diglycidyl ethers of bisphenol A or bisphenol F, said crosslinked hyaluronic acid or salt exhibiting water solubility and having a crosslinking index of 5 or more per 1000 repeating disaccharide units composed of glucuronic acid and N-acetylglucosamine.
The properties of hyaluronic acid were first determined by Karl Meyer in 1930. In particular, it is an anionic, nonsulfated glycosaminoglycan found throughout connective, epithelial, and neural tissues. As such, is it known to be a disaccharide polymer, composed of D-glucuronic acid and D-N-acetylglucosamine, linked via alternating β-1,4 and β-1,3 glycosidic bonds. It may be 25,000 disaccharide pairs in length, hence, it can range in molecular weight from 5,000 to 20,000,000 daltons; the foregoing considered, then hyaluronic acid's microdensity and its negative molecular charge will be greatly increased by further increasing its cross-linkage. This in turn, will directly affect its impact on the known cell receptors, for example, intercellular adhesion molecule-1 (ICAM-1). ICAM-1 is also believed to modulate inflammatory activation.
As used in this application, “non-cross linked hyaluronic acid” generally means refined forms of the naturally existing compounds. Also, “cross linked hyaluronic acid” means hyaluronic acid crosslinked with a polyfunctional epoxy compound. Further, “hyaluronic acid” refers to both non-cross linked hyaluronic acid and cross linked hyaluronic acid.
Embodiments of the present invention are simpler, safer, economical, more reliably enduring and effective at treating pain than the prior art. As there is no systemic absorption into the blood stream with the doses recommended, there is no potential for any related impaired cognition, psychotomimetic effects, or cardiovascular and/or cerebrovascular threat or instability; hence, rehabilitation may proceed unfettered.